Interactions between cells and the substrate to which they attach are important for many biological processes, including control of growth and differentiation. Loss or aberration of normal response in cancer cells to adhesive factors of the cell substratum may be involved in several ways in neoplastic growth, malignant invasion and metastasis. Recently we have studied, as a model for cell-substratum interactions, an adhesive glycoprotein isolated from human serum, which we termed "serum spreading factor" (SSF). We developed a bank of monoclonal antibodies which we used in the characterization of biochemical properties and biological activities of SSF, including identification of a platelet-associated form of SSF. Here we describe extensions of our studies in three categories: (1)\biochemical analyses of SSF and studies using monoclonal antibody to explore the relationship between structure and function of the molecule; (2)\use of serumfree cell culture to select and propagate variant cell lines with altered responses to one or more adhesive proteins (SSF, fibronectin), determination of associated biochemical changes, and examination of the effect of specific alterations of cell-substratum interactions in these cells on their ability to respond to extracellular growth regulators and form primary or metastatic tumors; (3)\studies on the role of SSF in platelet function and the role of platelets and platelet-associated adhesive factors in neoplastic and metastatic processes. We hope these studies will help us understand some of the factors involved in the emergence and spread of neoplastic disease in vivo.